Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals
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Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.
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Martinez-Cerdeno et al. found structural changes in offspring of pregnant mice injected with autoreactive IgG, including higher radial glial cell proliferation and increased brain and neuron size.
“A follow on study using the same technique showed structural changes in the offspring of pregnant mice injected with autoreactive IgG, including higher proliferation of radial glial cells and increased brain and neuron size”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Martinez-Cerdeno et al, 2016
Experimental mice exposed to maternal autoantibodies in utero show increased cell proliferation during cortical neurogenesis and increased neuronal and brain size in adulthood.
“Experimental mice exposed to maternal autoantibodies in utero show increased cell proliferation during cortical neurogenesis [184, 229] and increased neuronal and brain size in adulthood [229].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [229]
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- Authors
- Martínez-Cerdeño, V., Camacho, J., Fox, E., Miller, E., Ariza, J., Kienzle, D., Plank, K., Noctor, S. C., & Van de Water, J.
- Affiliations
- Shriners Hospitals for Children - Northern California (US)
- University of California, Davis (US)
- Corresponding author
- Martínez-Cerdeño, Verónica
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-12-22
- Volume
- 26
- Issue
- 1
- Pages
- 374-383
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC4677982
- OpenAlex
- W2017762661
- Cited by
- 63
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 5
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH101188, MH101188, MH094681, R01MH094681)
- National Institute of Environmental Health Sciences (P01ES011269)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, maternal autoantibodies, prenatal exposure, radial glia, cortical neurogenesis, neural progenitor proliferation, subventricular zone, brain size, neuron size, IgG transfer, autism risk factors
- MeSH terms
- Animals, Autistic Disorder, Autoantibodies, Cerebral Ventricles, Female, Nerve Tissue Proteins, Neurons, Pregnancy, Prenatal Exposure Delayed Effects, Neocortex, Mice, Neurogenesis, Neural Stem Cells
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